T Lymphocyte Regulation of Lysyl Oxidase in Diet-Induced Cardiac Fibrosis
- First Online:
Left ventricular diastolic dysfunction is an important predictor of prognosis and mortality of heart failure. Increased left ventricular stiffness can be associated with excessive myocardial fibrosis and increased cross-linked collagen by the enzyme lysyl oxidase (LOX). These cardiac extracellular matrix (ECM) remodeling processes are affected by T-lymphocyte function and phenotype. We sought to examine the role of T lymphocytes in myocardial LOX regulation in diet-induced fibrotic hearts. Female SCID mice, devoid of functional T lymphocytes, and wild-type (WT) C57BL/6 were treated with a high-fat high-simple carbohydrate (HFHSC) diet for 12 months. HFHSC-fed WT mice demonstrated a significant increase in the catalytic activity of myocardial LOX compared with respective controls. These changes coincided with a marked increase in ECM collagen cross-linking and impaired diastolic filling pattern. However, induction of LOX was minimal in the SCID mice compared with the WT group. Correspondingly fibrillar cross-linked collagen concentrations and diastolic dysfunction were less prominent in the SCID mice compared with the WT group. Our results suggest a role for T lymphocytes in this dietary induction of diastolic dysfunction through modulation of LOX-dependent collagen maturation.
KeywordsDiastolic dysfunction Lymphocytes Lysyl oxidase Cross-linked collagen
- 4.Badenhorst, D., Maseko, M., Tsotetsi, O. J., Naidoo, A., Brooksbank, R., Norton, G. R., et al. (2003). Cross-linking influences the impact of quantitative changes in myocardial collagen on cardiac stiffness and remodelling in hypertension in rats. Cardiovascular Research, 57, 632–641.CrossRefPubMedGoogle Scholar
- 10.Yang, B., Larson, D. F., Beischel, J., Kelley, R., Shi, J., & Watson, R. R. (2001). Validation of conductance catheter system for quantification of murine pressure-volume loops. International journal of surgical investigation, 14, 341–355.Google Scholar
- 23.Bock, O., Hoftmann, J., Theophile, K., Hussein, K., Wiese, B., Schlue, J., et al. (2008). Bone morphogenetic proteins are overexpressed in the bone marrow of primary myelofibrosis and are apparently induced by fibrogenic cytokines. American Journal of Pathology, 172, 951–960.CrossRefPubMedGoogle Scholar